This invention relates to a completely solubilized topical formulation of azelaic acid which is stable at normal temperatures. Topical azelaic acid formulations have been used to a wide range of physiological maladies including acne, hyperpigmentary dermatoses, hair loss, wrinkling, hyperhidrosis, non-acne inflammatory dermatoses, infectious cutaneous and ichthyosis.
However, the only topical formulations of azelaic acid presently known are dispersions. Dispersions deliver azelaic acid in an undissolved state. When applied to the skin, undissolved azelaic acid is not readily absorbed and as a result an excess of azelaic acid must be present to be effective. The higher the concentration of azelaic acid, the more likely irritation (burning, stinging and redness) to the skin will occur.
What is needed is a completely solubilized topical azelaic acid composition. Solubilized azelaic acid is much less likely to irritate the skin because azelaic acid in a dissolved state is much more readily absorbed by the skin than in the undissolved states found in dispersions. Better absorption means less azelaic acid need be present in the formulation to be effective thereby lowering the risk of irritation to the skin.
While azelaic acid is somewhat soluble in water, cosmetic oils and alcohols, each of these solvents has serious limitations. Thus, water only marginally dissolves azelaic acid so that a water and azelaic acid solution would contain a maximum of about 0.24% by weight (w/w) azelaic acid, not likely enough to be effective. Azelaic acid has little or no solubility in cosmetic oils. Alcohols are good solvents but are unsatisfactory because large amounts of alcohol e.g., isopropyl alcohol, in a topical composition has the undesirable side effect of drying the skin. Indeed, some alcohols e.g., ethyl alcohol, render azelaic acid unstable at normal temperatures resulting in a totally ineffective composition.
U.S. Pat. Nos. 4,292,326 (Nazzaro-Porro, Sep. 29, 1981), 4,386,104 (Nazzaro-Porro, May 31, 1983), and 4,818,768 (Nazzaro-Porro, Apr. 4, 1989) describe azelaic acid as well as other dicarboxylic acids in the treatment of acne and melanocyclic hyperpigmentary dermatoses. The azelaic acid is dispersed in a cream base.
U.S. Pat. Nos. 4,713,394 (1Thornfeldt, Dec. 15, 1987) and 4,885,282 (Thornfeldt, Dec. 5, 1989) describe of azelaic acid as well as other dicarboxylic acids used in the treatment of nonacne inflammatory dermatoses and infectious cutaneous diseases such as rosacea, perioral dermatitis, eczema, seborrheic dermatitis, psoriasis, tinea cruris, flat warts, and alopecia areata. One of Thornfeldt's formulations comprises azelaic acid disposed in a large proportion of ethanol. While ethyl alcohol dissolves azelaic acid, it also renders the azelaic acid unstable at normal temperatures meaning that it will not provide a marketable product. Thornfeldt's second formulation comprises a complete dispersion of azelaic acid.
An emulsion containing 10-20% concentration of azelaic acid in a base of water, apple pectin and sunflower oil was taught by Berova, N., et al. in "Hypoallergic Cosmetic Emulsion with Azelaic Acid for Prophylaxy and Treatment of Acne Vulgaris," Berova, N., Nkiolova, A., Kratchanov, Chr., and Popova, M., Journal of Applied Cosmetology, vol. 12, no. 3, p. 51 (1994). Berova et al. attribute the mildness of their formulation to the use of natural ingredients like apple pectin and sunflower oil instead of non-natural substances in the azelaic acid vehicle. The emulsion taught by Berova et al. is not completely solubilized and suffers from the same problem as do the Nazzaro-Porro and Thornfeldt formulations, the weight percent of azelaic acid in the formulation is higher than needed because the azelaic acid is not completely solubilized.
Venkateswaran U.S. Pat. No. 5,549,888 teaches a solution of active ingredients which includes azelaic acid and is partially solubilized by a glycol. It uses glycol in combination with ethyl alcohol to solubilize the azelaic acid. As stated previously, the presence of ethyl alcohol with azelaic acid can destabilize the azelaic acid. Moreover, because the composition contains ethyl alcohol, formulation of a non-drying, aesthetically pleasing formulation would be difficult. Venkateswaran also teaches that the formulation has a pH between 2.5 and 4.0. This low pH range can have an irritating effect on the skin.
The art has yet to find a formulation for completely solubilizing azelaic acid at normal temperatures without sacrificing the stability of the solubilized azelaic acid. Solubilized azelaic acid must remain stable at normal temperatures in order to provide a marketable product.
Without a stable, completely solubilized formula of azelaic acid, the benefits of azelaic acid are unavailable to many users who experience the burning, stinging and redness of the skin associated with exposure to high levels of undissolved dispersed azelaic acid having an inherent low pH. The present invention provides a completely solubilized and stable formulation of azelaic acid in a glycol base at normal temperatures exhibiting a tolerable pH of 4 or greater and having a shelf life which enables a marketable product to be produced and reduces the amount of azelaic acid the user must be exposed to in order to enjoy its benefits.